Endogenous Tim-1 promotes severe systemic autoimmunity and renal disease MRL-Fas(lpr) mice

Yuji Nozaki, Arthur Richard Kitching, Hisaya Akiba, Hideo Yagita, Koji Kinoshita, Masanori Funauchi, Itaru Matsumura

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)


The T-cell immunoglobulin mucin 1, also known as kidney injury molecule-1, modulates CD4+ T-cell responses and is also expressed by damaged proximal tubules within the kidney. Both Th subset imbalance (Th1/Th2/Th17) and regulatory T-cell and B-cell alterations contribute to the pathogenesis of autoimmune disease. This study investigated the effects of an inhibitory anti-T-cell immunoglobulin mucin 1 antibody (RMT1-10) in lupus-prone MRL-Fas(lpr) mice. MRL-Fas(lpr) mice were treated with RMT1-10 or a control antibody intraperitoneally twice weekly from 3 mo of age for 16 wk. RMT1-10 treatment significantly improved survival, limited the development of lymphadenopathy and skin lesions, preserved renal function and decreased proteinuria, reduced serum anti-DNA antibody levels, and attenuated renal leukocyte accumulation. Th1 and Th17 cellular responses systemically and intrarenally were reduced, but regulatory T and B cells were increased. RMT1-10 treatment also reduced glomerular immunoglobulin and C3 deposition and suppressed cellular proliferation and apoptosis. Urinary excretion and renal expression of kidney injury molecule-1 was reduced, reflecting diminished interstitial injury. As RMT1-10 attenuated established lupus nephritis, manipulating immune system T-cell immunoglobulin mucin 1 may represent a therapeutic strategy in autoimmune diseases affecting the kidney.
Original languageEnglish
Pages (from-to)F1210 - F1221
Number of pages12
JournalAmerican Journal of Physiology-Renal Physiology
Issue number10
Publication statusPublished - 2014

Cite this